Archive ScienceWatch



Caren C. Helbing talks with and answers a few questions about this month's New Hot Paper in the field of Plant & Animal Science. The author has also sent along images of their work.
Helbing Article Title: The bactericidal agent triclosan modulates thyroid hormone-associated gene expression and disrupts postembryonic anuran development
Authors: Veldhoen, N;Skirrow, RC;Osachoff, H;Wigmore, H;Clapson, DJ;Gunderson, MP;Van Aggelen, G;Helbing, CC
Volume: 80
Issue: 3
Page: 217-227
Year: DEC 1 2006
* Univ Victoria, Dept Biochem & Microbiol, POB 3055,Stn CSC, Victoria, BC V8W 3P6, Canada.
(addresses have been truncated)

 Why do you think the paper is highly cited?

Triclosan is found in so many consumer products. Finding out that triclosan can change how an important hormone works in the body at levels that we and animals are exposed to is relevant to all of us.

 Does it describe a new discovery, methodology, or synthesis of knowledge?

We focused on a native frog species and introduced sampling and analysis methodologies that have broad applicability to other wildlife species.

 Would you summarize the significance of your paper in layman's terms?

Frogs act like "canaries in the coalmine" in water and wetlands. They are very sensitive indicators of pollutants and tell us about the health of our environment. They also tell us a lot about ourselves when it comes to thyroid hormones. When a tadpole changes into a frog, thyroid hormones trigger that amazing change.

Figure 1: +details
Click figure to enlarge and read description.
Figure 2:
Click figure to enlarge and read description.
Photo credit (all):
Dennis Helbing

In humans, many of the changes that occur in the frog tadpole are mirrored in the developing fetus. Thyroid hormones are really important in proper brain development for example. Thyroid hormones work in a similar way in frogs, humans, and other vertebrates; so if triclosan is affecting how they work in frogs, it is possible that other animals, including humans, could be affected too.

 How did you become involved in this research, and were there any problems along the way?

I have a long-standing interest in how cells respond to their environment. As a graduate student, I was introduced to the amazing changes that frogs experience during their metamorphosis and I was hooked! I became fascinated by how a single hormone, the thyroid hormone, can cause so many organs and tissues to change in so many different ways—legs and lungs grow, the tail and gills disappear, the brain and liver remodel—all in a coordinated way, to turn a tadpole into a frog.

The fact that different tissues and organs respond to hormones in their own ways also means that they could have different sensitivities to chemicals that disrupt thyroid hormone action.

We still don't know how all this works, but a lot of it has to do with how the genome (genetic code) is accessed and how proteins are affected. A big challenge was to develop the right tools and methods to be able to sense changes to proteins and to identify which genes may be important. We're still working on improving this approach.

 Where do you see your research leading in the future?

A growing number of substances released into the environment have been identified as disruptors of critical, normal hormone-dependent mechanisms in humans and animals. These endocrine disruptors come from a variety of sources such as plants, pharmaceuticals, pesticides, environmental pollutants, and industry. The impact of these diverse compounds is far-reaching; from effects on human and wildlife health to contributing to wildlife population declines and resultant ecosystem imbalances.

Particularly vulnerable are those life stages where considerable modeling or remodeling of existing body plans occurs such as in embryonic development, metamorphosis, infancy, childhood and lactation. Thus, exposure to endocrine disruptors at any of these critical stages could result in permanent dysfunction, increased susceptibility to certain cancers and reproductive problems reaching as far as multiple generations.

It is critical to have the appropriate tools in place to identify the existence of endocrine disruptors in water samples (where most will eventually end up) and to properly evaluate any endocrine disruptor risk in chemicals that are to be released into our environment. Amphibians, fish, marine mammals, bivalves, and other wildlife species are our sentinels.

By developing and using a wide range of molecular approaches that include multi-species DNA arrays, quantitative real time PCR, and proteomic techniques, we are uncovering the mechanisms of action of potential endocrine disruptors and are gaining insight into how hormones function in different tissues and species.

Critical to the normal development and maintenance of an organism's health is ensuring that an appropriate balance is struck between two disparate processes: cell proliferation and programmed cell death. Although a great deal is understood about the machinery involved in both processes, the factors that are critical in determining which pathway cells take is not known, particularly when a single stimulus can simultaneously elicit both outcomes.

A classic example of this is the normal postembryonic development of the frog. A marked elevation of thyroid hormone (TH) levels triggers the rapid and dramatic metamorphosis of the aquatic tadpole to a terrestrial juvenile frog. The most obvious changes observed are the disappearance of the tail and the growth of the legs. This program focuses on understanding how the tail "knows" that it should die after receiving the triggering message from TH.

We are particularly interested in the role that cell cycle regulating proteins and phosphorylation may be involved in determining cellular outcome. Since frogs are vertebrates, the knowledge obtained by studying them can be easily applied to humans and, hence, will give us important clues in the control of cell death and cancer.

There are many other chemicals and mixtures of chemicals that need to be tested for possible effects on thyroid hormone action. We also need to get a better idea on what part of the thyroid hormone signaling pathways are most vulnerable to disruption. We need to develop new ways to define what the pathways are in different tissues. In order to do this, we are currently devising approaches based upon the power of transcriptomics, proteomics, and metabolomics. These approaches will also help us to understand why frog populations are declining and guide us in taking steps to protect our environment.

 Do you foresee any social or political implications for your research?

The safety and quality of our environment and the products that we use are of primary importance to people and wildlife alike. Our research is important in helping to better assess risks posed within our complex environment and also to work towards achieving sustainability and stewardship of our waterways and water resources.

Caren Helbing, Ph.D.
Associate Professor and Michael Smith Foundation for Health Research Scholar
Department of Biochemistry and Microbiology
University of Victoria
Victoria, BC, Canada

Keywords: triclosan, postembryonic anuran development, frog populations, frog tadpole, thyroid hormones, hormone-dependent, endocrine disruptors, water samples, plants, pharmaceuticals, pesticides, environmental pollutants, industrial pollutants, wildlife population declines, ecosystem imbalances, embryonic development, metamorphosis, infancy, childhood and lactation, amphibians, fish, marine mammals, bivalves, multi-species DNA arrays, quantitative real time PCR, proteomic techniques, thyroid hormone (TH), transcriptomics, proteomics, metabolomics, waterways, water resources


2008 : May 2008 - New Hot Papers : Caren C. Helbing